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A new approach to assessment of reproductive losses of the first trimester of pregnancy

https://doi.org/10.29413/ABS.2021-6.3.4

Abstract

 Background. At present, the role of cytomegalovirus infection in the disruption of acental formation and associated pathological conditions of the fetus is bvious, which are based on oxidative and inflammatory reactions that cause disruption of igration and invasion of trophoblasts, angiogenic modulation of placental and uterine vessels.

Objective: To analyze the quantitative indicators of hypoxia-inducible factor 1α, α-tocopherol and docosahexaenoic acid in the peripheral blood in comparison with morphological changes in the placenta and uterine mucosa in seropositive women with spontaneous abortion associated with reactivation of ytomegaloviral infection.

Methods: Studies were carried out at 7-9 weeks of gestation. 67 observations were analyzed, including 35 seropositive women in the first trimester with spontaneous abortion associated with reactivation of cytomegaloviral infection and 32 healthy seronerative women with voluntary termination of pregnancy. Stabilized blood from vein, epithelium of the inner surface of the cheek, cervical canal, urine, villous chorion, and uterine mucosa were used as the test material. Enzyme immunoassay was used to detect serological markers of cytomegaloviral infection (CMV-IgG/IgM antibodies, CMV-IgG avidity), hypoxia-induced factor 1α, α-tocopherol – by fluorometric method, PCR (polymerase chain reaction) in real time – DNA CMV, the method of gas-liquid chromatography – docosahexaenoic acid, histological methods – the general plan of the structure of the chorionic villus and the mucous membrane of the uterus.

Results: In seropositive women with spontaneous abortion associated with reactivation of cytomegaloviral infection, the average of hypoxia-induced  factor 1α was 1.54 times higher, α-tocopherol and docosahexaenoic acid were 1.71 times lower and 1.40 times lower (p < 0.001, respectively) than in the group of eronegative women. Strong inverse correlations were revealed. Morphologically, there were signs of delayed formation of villi, decidualization of the endometrial stroma and the formation of uteroplacental vessels. 

Conclusion. In seropositive women with spontaneous abortion associated with reactivation of cytomegaloviral infection, a strong association of high HIF-1α values with decrease in α-tocopherol and docosahexaenoic acid in the peripheral blood was revealed, which can be considered as an unfavorable factor in the disruption of placenta formation. 

About the Authors

N. A. Ishutina
Far Eastern Scientific Center of Physiology and Pathology of Respiration
Russian Federation

 ScD, PhD, Leading staff scientist of Laboratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases

22 Kalinina Str., Blagoveshchensk, 675000, Russian Federation

Tel.: (4162) 772815 



I. A. Andrievskaya
Far Eastern Scientific Center of Physiology and Pathology of Respiration
Russian Federation

 DSc, PhD, head of laboratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases,

22 Kalinina Str., Blagoveshchensk, 675000, Russian Federation

Tel.: (4162) 772815 



N. G. Prikhodko
Far Eastern Scientific Center of Physiology and Pathology of Respiration
Russian Federation

 postgraduate student of laboratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases

22 Kalinina Str., Blagoveshchensk, 675000, Russian Federation

Tel.: (4162) 772815 



References

1. Makarov IO, Voyevodin SM, Shemanayeva TV. Features of placental insufficiency in the presence of intrauterine infection. Vrach-aspirant. 2012; 1. 2 (50): 253–258. (In Russian)

2. Nadeyev AP, Travin MA, Drobinskaya AN, Karpov MA, Telyatnikova NV, Zhukova VA., et al. Features of placenta infection with cytomegalovirus and virus of herpes simplex of the second type at the full-term pregnancy. Journal of Siberian Medical Sciences. 2015; 3: 83. (In Russian)

3. Andriyevskaya IA, Lutsenko MT, Petrova KK, Kochegarova EYu, Prikhod»ko NG. Placental growth factor as a marker of the threatened early miscarriage in women with cytomegalovirus infection. Byulleten» fiziologii i patologii dykhaniya. 2017; 64: 55–59. doi: 10.12737/article_59360cc93f6447.76641762 (In Russian)

4. Charostad J, Mokhtari-Azad DV, Mph MT, Ph D, Yavarian J, Ghavami N, et al. Detection of human herpes viruses 1–5 in iscarriage: A case-control study. Int J Reprod Biomed. 2020; 18 (7): 501–508. doi: 10.18502/ijrm.v13i7.7367

5. Li JM, Zhang HF, Zhang XQ, Huang GL, Huang HZ, Yu WW. Genetic mechanism associated with congenital cytomegalovirus infection and analysis of effects of the infection on pregnancy outcome. Genet Mol Res. 2015; 14 (4): 13247–13257. doi: 10.4238/2015.October.26.21

6. Njue A, Coyne C, Margulis AV, Wang D, Marks MA, Russell K, et al. The Role of Congenital Cytomegalovirus Infection in Adverse Birth Outcomes: A Review of the Potential Mechanisms. Viruses. 2020; 13 (1): 20. doi: 10.3390/v13010020

7. Pass RF, Arav-Boger R. Maternal and fetal cytomegalovirus infection: diagnosis, management, and prevention. F1000Res. 2018; 7: 255. doi: 10.12688/f1000research.12517.1

8. Strizhakov AN, Kushlinskiy NE, Timokhina EV, Tarabrina TV. The role of angiogenic growth factors in predicting placental insufficiency. Voprosy ginekologii, akusherstva i perinatologii. 2009; 8 (4): С. 5–11. (In Russian)

9. Mikhaylin ES, Tolibova GKh, Tral» TG. Morfological and functional features of placentas in minor women. Zhurnal akusherstva i zhenskikh bolezney. 2016; 65 (5): 41–48. doi.org/10.17816/JOWD65541-48. (In Russian)

10. Bol»shakova MV, Bezhenar» VF, Pavlova NG, Pastushenkov VL, Gabayeva MM. Modern ideas about the pathogenesis of fetal hypoxia and the role of hypoxia-inducible factor (HIF) in it. Akusherstvo i ginekologiya Sankt-Peterburga. 2019; 1: 19–24. (In Russian)

11. Macklin PS, McAuliffe J, Pugh CW, Yamamoto A. Hypoxia and HIF pathway in cancer and the placenta. Placenta. 2017; 56: 8–13. doi: 10.1016/j.placenta.2017.03.010

12. Yu N, Wu JL, Xiao J, Fan L, Chen SH, Li W. HIF-1α regulates angiogenesis via Notch1/STAT3/ETBR pathway in rophoblastic cells. Cell Cycle. 2019; 18 (24): 3502–3512. doi: 10.1080/15384101.2019.1689481

13. Pandya AD, Das MK, Sarkar A, Vilasagaram S, Basak S, Duttaroy AK. Tube formation in the first trimester placental trophoblast cells: Differential effects of angiogenic growth factors and fatty acid. Cell. Biol. Int. 2016; 40 (6): 652–661. doi: 10.1002/cbin.10601

14. Kasture V, Sundrani D, Dalvi S, Swamy M, Kale A, Joshi S. Maternal omega-3 fatty acids and vitamin E improve placental angiogenesis in late-onset but not early-onset preeclampsia. Mol. Cell. Biochem. 2019; 461 (1-2): 159–170. doi: 10.1007/s11010-019-03599-4

15. Taneda S, Honda K, Tomidokoro K., Uto K, Nitta K, Oda H. Eicosapentaenoic acid restores diabetic tubular injury through regulating oxidative stress and mitochondrial apoptosis. Am. J. Physiol. Renal. Physiol. 2010; 299 (6): F1451-F1461. doi:10.1152/ajprenal.00637.2009

16. Rathod RS, Khaire AA, Kale AA, Joshi SR. Maternal omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalizes angiogenic markers in the pup brain at birth. Int. J. Dev Neurosci. 2015; 43 (1): 43–49. doi:10.1016/j.ijdevneu.2015.04.006

17. Hansen LG, Warwich WI. Flurometric micromethod for serum tocoferol. Am. J. Chen Pathology. 1966; 36 (1): 137–138.

18. Morozova OL, Mal»tseva LD, Makarova VD. VEGF asa biomarker for hypoxia in kidney injury of different origins. Patogenez. 2018; 16 (2): 62–69. doi: 10.25557/2310–0435.2018.0262–69 (In Russian)

19. Azliana AF, Zainul-Rashid MR, Chandramaya SF, Farouk WI, Nurwardah A, Wong YP, Tan GC. Vascular endothelial growth factor expression in placenta of hypertensive disorder in pregnancy. Indian J Pathol Microbiol. 2017; 60 (4): 515–520. doi: 10.4103/IJPM.IJPM_376_16

20. Makarov OV, Volkova EV, Lysyuk EYu, Kopylova YuV. Fetoplacental angiogenesis in pregnant women with placental insufficiency. Akusherstvo, ginekologiya, reproduktsiya. 2013; 7 (3): 13–19. (In Russian)

21. Zhao H, Narasimhan P, Kalish F, Wong RJ, Stevenson DK. Dysregulation of hypoxia-inducible factor-1α (Hif1α) expression in the Hmox1-deficient placenta. Placenta. 2020; 99: 108–116. doi: 10.1016/j.placenta.2020.07.015

22. Levchenkova OS, Novikov VE. Inducers of the regulatory factor to hypoxia adaptation. Rossiyskiy mediko-biologicheskikh vestnik im. akad. I. P. Pavlova. 2014; 2: 135–145. (In Russian)

23. Mel»nik AA. Hypoxia-inducible factor for the treatment of anemia in chronic kidney disease. Pochki. 2018; 7 (4): 311–321. doi: 10.22141/2307-1257.7.4.2018.148522 (In Russian)

24. Bezhenar» VF, Pavlova NG, Bol»shakova MV, Pastushenkov VL, Karev VE. Expression of hypoxia-induced factor (HIF1α) in placentas with chronic placental insufficiency at the end of pregnancy. Ural»skiy meditsinskiy zhurnal. 2020; 5 (188): 141–145. doi: 10.25694/URMJ.2020.05.29 (In Russian)

25. Ishutina NA, Andrievskaya IA, Dorofienko NN. Malon dialdehyde and tumor necrosis factor alpha at cytomegalovirus infection during pregnancy. Byulleten» fiziologii i patologii dykhaniya. 2015; 55: 78–81. (in Russian)

26. de Wit RH, Mujić-Delić A, van Senten JR, Fraile-Ramos A, Siderius M, Smit MJ. Human cytomegalovirus encoded chemokine receptor US28 activates the HIF-1α/PKM2 axis in glioblastoma cells. Oncotarget. 2016; 7 (42): 67966–67985. doi: 10.18632/oncotarget.11817

27. He C, Shan N, Xu P, Ge H, Yuan Y, Liu Y, et al. Hypoxiainduced Downregulation of SRC-3 Suppresses Trophoblastic Invasion and Migration Through Inhibition of the AKT/mTOR Pathway: Implications for the Pathogenesis of Preeclampsia. Sci Rep. 2019; 9 (1): 10349. doi: 10.1038/s41598-019-46699-3

28. Ishutina NA, Dorofienko NN. Lipid peroxidation in regnancy complicated by cytomegalovirus infection. Byulleten» fiziologii i patologii dykhaniya. 2014; 54: 56–59. (In Russian)

29. Kasimanickam RK, Kasimanickam VR, Haldorson GJ, Tibary A. Effect of tocopherol supplementation during last trimester of pregnancy on mRNA abundances of interleukins and angiogenesis in ovine placenta and uterus. Reprod. Biol. Endocrinol. 2012; 10: 4. doi: 10.1186/1477-7827-10-4

30. Kasimanickam RK, Kasimanickam VR, Rodriguez JS, Pelzer KD, Sponenberg PD, Thatcher CD. Tocopherol induced angiogenesis in placental vascular network in late pregnant ewes. Reprod. Biol. Endocrinol. 2010; 8: 86. doi.org/10.1186/1477-7827-8-86

31. Basak S, Das MK, Duttaroy AK. Fatty acid-induced angiogenesis in first trimester placental trophoblast cells: possible roles of cellular fatty acid-binding proteins. Life Sci. 2013; 93 (21): 755–762. doi: 10.1016/j.lfs.2013.09.024

32. Rada CC, Murray G, England SK. The SK3 channel promotes placental vascularization by enhancing secretion of angiogenic factors. American Journal of physiology, endocrinology and metabolism. 2014; 307 (10): E935–943. doi: 10.1152/ajpendo.00319.2014

33. Irwin DC, McCord JM, Nozik-Grayck E, Beckly G, Foreman B, Sullivan T, White M, T Crossno JJr, Bailey D, Flores SC, Majka S, Klemm D, van Patot MC. A potential role for reactive oxygen species and the HIF-1alpha-VEGF pathway in hypoxiainduced pulmonary vascular leak. Free Radic Biol Med. 2009; 47 (1): 55–61. doi: 10.1016/j.freeradbiomed.2009.03.027


Review

For citations:


Ishutina N.A., Andrievskaya I.A., Prikhodko N.G. A new approach to assessment of reproductive losses of the first trimester of pregnancy. Acta Biomedica Scientifica. 2021;6(3):43-52. (In Russ.) https://doi.org/10.29413/ABS.2021-6.3.4

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